Pericyte in the adult muscle satellite cell niche: A key player in steady state and recovery

Abstract

Introduction/objectives Muscle growth and regeneration are supported by muscle satellite cells (muSCs) that reside beneath the myofiber basement membrane in close proximity to capillaries. Pericytes play a key role in the microvascular niche of muSCs during post-natal stages of muscle growth, by promoting post-natal myogenesis through IGF-1 and inducing muSC quiescence ending the accretion phase through Angiopoietin-1. Since 90% of capillaries have pericyte coverage at the end of muscle growth, we investigated the role of pericytes in the adult muSC niche. Materials/Patients and methods We used TNAP-CreERT2 mice crossed with R26RDTRstoploxP/stoploxP, Angiopoietin-1loxP/loxP, and R26RmTloxPmG/loxPmG animals to generate respectively conditional models for diphteria toxin-induced muscle depletion of microvascular cells, ablation of microvascular Angiopoietin-1 and fluorescent tracing of microvascular cells. Results Conditional muscle pericyte depletion could not be used due to extensive, presumably ischaemic, muscle necrosis. In contrast, selective Cre recombinase ablation of Angiopoietin-1 gene in TNAP+ pericytes induced release of adult mSCs from quiescence. Following chemical injury, the ablation caused delayed muscle regeneration with persistently cycling Pax7+ mSCs. Selective type 2 fiber hypotrophy was observed consistently with prominent association of TNAP-expressing microvessels with type 2 fibers observed in TNAP-GFP reporter mice. Conclusions We conclude that pericytes associated with endothelial cells exert paracrine effects on adjacent myogenic cells that participate in maintaining adult muscle homeostasis and during muscle repair.